In-vitro diagnostic devices are widely used. Useful diagnostic assay devices depend on biospecific affinity reactions for detecting, isolating, and/or separating cells, proteins, bacteria, viruses, nucleic acid sequences, and various other materials or compounds of interest. Many medical diagnostic tests require the detection, isolation, and/or measurement of specific compounds present in biological fluids such as blood, saliva, and urine.
Diagnostic tests can be conducted using a variety of devices, for example, electronic devices, biosensors, lateral flow devices, test strips, and test cards, among others. Often the necessary materials to conduct a test are provided in the form of a test kit, which may include a particular testing device. Some testing devices include the reagent or reagents necessary to perform a particular test. For other testing devices, the reagent(s) is obtained separately and used in connection with the testing device.
Substances which can be detected, measured, and/or isolated using an in-vitro diagnostic device include, for example, glucose; cholesterol; proteins, for example, various enzymes, such as amylase and creatine kinase; substances-of-abuse, for example, drugs regulated by law with respect to possession and use, such as methamphetamines; cells; bacteria; viruses; and nucleic acid sequences; among others. For example, pregnancy testing can be conducted using test strips to detect human chorionic gonadotropin (hCG). Such a test is described in U.S. Pat. Nos. 6,403,298 and 4,496,654. Also, diabetics and health care professionals use test strips for measuring blood glucose levels. U.S. Pat. No. 6,270,637 describes an electrochemical biosensor blood glucose test strip. Diagnostic testing, as described in U.S. Pat. No. 5,846,751, is used to detect helicobacter pylori bacterium in the human stomach to diagnose gastric disorders and duodenal ulcer disease. U.S. Pat. No. 6,645,731 describes the isolation of cancer cells from a biochemical matrix.
Lateral flow testing devices are commonly used. Typically, a lateral flow device includes a test strip, on which one or more reagents are present. To use the lateral flow testing device, a fluid sample is deposited onto the strip and migrates by capillary action along the strip where chemical reactions take place depending upon the presence or absence of the analyte in situ. Often, at least one reagent is included which manifests a detectable signal, for example a color change, in the presence of a minimal amount of the analyte of interest.
To fabricate test strips, aqueous solutions containing a reagent, for example, enzymes or antibodies, are localized on a supporting layer, which is a solid material, such as membrane support, an electrochemical sensor, cellulose or paper. The reagents are selected as necessary or helpful in detection of the analyte in question. Typically, the reagent is placed on the membrane by spraying, coating, or striping and then dried.
Other diagnostic testing devices require the use of various aqueous reagents. The reagents are typically applied by pipette directly to the sample to be tested.
Reagents can be expensive. Therefore, waste of reagents is undesirable. Conventional preparation techniques for test strips, such as spraying, coating or striping, can result in loss of reagent. Additionally, it is difficult to control the amount of reagent on the test strip using conventional techniques. Further, aqueous reagents can be cumbersome to handle. Some reagents are unstable in aqueous form and may require specialized storage, such as refrigeration.
Magnetic particles that have been functionalized with specific chemical reactive moieties also are known for use as reagents in immunoassays. In these assays, biochemical complexes are separated and isolated based on magnetic properties. U.S. Pat. No. 6,120,856 refers to the use of ferro fluids in diagnostic techniques including imunoassays, cell separation, toxicity testing, food testing, and environmental analysis. U.S. Pat. No. 6,672,458 describes the uses of functionalized paramagnetic particles for the separation and isolation of nucleic acid (DNA and RNA) from amplification techniques. Following amplification the cells are lysed and specific nucleic acid sequences are complexed to the functionalized paramagnetic particles. The paramagnetic particles with the bound nucleic acid are separated from the remaining solution using the magnetic properties of the complex.
However, it has been difficult to control the concentration of the magnetic particles due to static effects on the glass and plastic containers used in conventional diagnostic techniques. Plastic containers made from polystyrene and polypropylene are know to retain a static charge. The static charge on test tubes and other components causes problems in dispensing quantitative amounts of particles due to particle attraction to plastic and glass surfaces.
Accordingly, it would be desirable to provide reagent compositions and diagnostic devices that minimize or eliminate the above problems.